Rosiane Aparecida Miranda, Beatriz Souza da Silva, Iala Milene Bertasso, Luana Lopes de Souza, Edgar Mendes Souza Wan Der Maas, Jones Bernardes Graceli, Leandro Miranda-Alves, Egberto Gaspar de Moura, Patricia Cristina Lisboa
{"title":"母体接触三丁基锡会改变女性生殖系统的发育。","authors":"Rosiane Aparecida Miranda, Beatriz Souza da Silva, Iala Milene Bertasso, Luana Lopes de Souza, Edgar Mendes Souza Wan Der Maas, Jones Bernardes Graceli, Leandro Miranda-Alves, Egberto Gaspar de Moura, Patricia Cristina Lisboa","doi":"10.1530/JOE-24-0357","DOIUrl":null,"url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Tributyltin (TBT) is a toxic compound used in antifouling paints and known for its endocrine-disrupting properties, including female reproductive dysfunction. We hypothesized that TBT exposure during gestation and lactation induces long-term reproductive alterations in female offspring. Pregnant Wistar rats were orally exposed from gestational day 7 to the end of lactation to 0.01% ethanol (control), TBT 100 ng/kg, or TBT 1000 ng/kg body weight. Female offspring were evaluated at postnatal days (PND) 21, 45, and 180 for biometric, hormonal, and ovarian parameters. Birth weight was reduced in the TBT100ng group, and body weight was reduced by PND180 in the TBT1000ng group. At PND45, testosterone increased in both TBT groups, while FSH decreased in the TBT100ng group. Estrous cyclicity irregularities, such as a prolonged metestrus-diestrus phase, were noted in the TBT1000ng group. Ovarian analysis showed increased cystic and atretic follicles at PND21 and PND45. Reduction in primordial follicles (TBT100ng) and corpora lutea (both TBT groups) was observed at PND180, along with ovarian fibrosis. TBT exposure led to age- and dose-dependent disruptions in ovarian follicle dynamics: initial increases in healthy follicles at PND21, followed by elevated unhealthy follicles and reduced healthy ones at later stages. At PND21, both TBT doses increased ERα expression, while TBT100ng increased AR expression. These changes were accompanied by a persistent increase in ovarian mast cells and elevated IL-6 protein expression, particularly at PND21 and PND180. Thus, maternal TBT exposure disrupts ovarian development and function, potentially increasing susceptibility to abnormal conditions such as polycystic ovary syndrome and primary ovarian insufficiency later in life.</p>","PeriodicalId":15740,"journal":{"name":"Journal of Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Maternal exposure to tributyltin alters female reproductive system development.\",\"authors\":\"Rosiane Aparecida Miranda, Beatriz Souza da Silva, Iala Milene Bertasso, Luana Lopes de Souza, Edgar Mendes Souza Wan Der Maas, Jones Bernardes Graceli, Leandro Miranda-Alves, Egberto Gaspar de Moura, Patricia Cristina Lisboa\",\"doi\":\"10.1530/JOE-24-0357\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Tributyltin (TBT) is a toxic compound used in antifouling paints and known for its endocrine-disrupting properties, including female reproductive dysfunction. We hypothesized that TBT exposure during gestation and lactation induces long-term reproductive alterations in female offspring. Pregnant Wistar rats were orally exposed from gestational day 7 to the end of lactation to 0.01% ethanol (control), TBT 100 ng/kg, or TBT 1000 ng/kg body weight. Female offspring were evaluated at postnatal days (PND) 21, 45, and 180 for biometric, hormonal, and ovarian parameters. Birth weight was reduced in the TBT100ng group, and body weight was reduced by PND180 in the TBT1000ng group. At PND45, testosterone increased in both TBT groups, while FSH decreased in the TBT100ng group. Estrous cyclicity irregularities, such as a prolonged metestrus-diestrus phase, were noted in the TBT1000ng group. Ovarian analysis showed increased cystic and atretic follicles at PND21 and PND45. Reduction in primordial follicles (TBT100ng) and corpora lutea (both TBT groups) was observed at PND180, along with ovarian fibrosis. TBT exposure led to age- and dose-dependent disruptions in ovarian follicle dynamics: initial increases in healthy follicles at PND21, followed by elevated unhealthy follicles and reduced healthy ones at later stages. At PND21, both TBT doses increased ERα expression, while TBT100ng increased AR expression. These changes were accompanied by a persistent increase in ovarian mast cells and elevated IL-6 protein expression, particularly at PND21 and PND180. Thus, maternal TBT exposure disrupts ovarian development and function, potentially increasing susceptibility to abnormal conditions such as polycystic ovary syndrome and primary ovarian insufficiency later in life.</p>\",\"PeriodicalId\":15740,\"journal\":{\"name\":\"Journal of Endocrinology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Endocrinology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1530/JOE-24-0357\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Endocrinology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1530/JOE-24-0357","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"Print","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Maternal exposure to tributyltin alters female reproductive system development.
Graphical abstract:
Abstract: Tributyltin (TBT) is a toxic compound used in antifouling paints and known for its endocrine-disrupting properties, including female reproductive dysfunction. We hypothesized that TBT exposure during gestation and lactation induces long-term reproductive alterations in female offspring. Pregnant Wistar rats were orally exposed from gestational day 7 to the end of lactation to 0.01% ethanol (control), TBT 100 ng/kg, or TBT 1000 ng/kg body weight. Female offspring were evaluated at postnatal days (PND) 21, 45, and 180 for biometric, hormonal, and ovarian parameters. Birth weight was reduced in the TBT100ng group, and body weight was reduced by PND180 in the TBT1000ng group. At PND45, testosterone increased in both TBT groups, while FSH decreased in the TBT100ng group. Estrous cyclicity irregularities, such as a prolonged metestrus-diestrus phase, were noted in the TBT1000ng group. Ovarian analysis showed increased cystic and atretic follicles at PND21 and PND45. Reduction in primordial follicles (TBT100ng) and corpora lutea (both TBT groups) was observed at PND180, along with ovarian fibrosis. TBT exposure led to age- and dose-dependent disruptions in ovarian follicle dynamics: initial increases in healthy follicles at PND21, followed by elevated unhealthy follicles and reduced healthy ones at later stages. At PND21, both TBT doses increased ERα expression, while TBT100ng increased AR expression. These changes were accompanied by a persistent increase in ovarian mast cells and elevated IL-6 protein expression, particularly at PND21 and PND180. Thus, maternal TBT exposure disrupts ovarian development and function, potentially increasing susceptibility to abnormal conditions such as polycystic ovary syndrome and primary ovarian insufficiency later in life.
期刊介绍:
Journal of Endocrinology is a leading global journal that publishes original research articles, reviews and science guidelines. Its focus is on endocrine physiology and metabolism, including hormone secretion; hormone action; biological effects. The journal publishes basic and translational studies at the organ, tissue and whole organism level.